An acute injection of ascorbic acid (120mg/kg, i.p.) or chronic treatment with isoproterenol (4 microns/kg,l.m., 3 times a day for 7 days) reduced airway sensitivity in guinea pigs to histamine and isoproterenol by 4-fold. Treatments also abolished the effects of beta-adrenergic blockade with propranolol (10mg/kg, i.p.). Sensitivities to histamine, isoproterenol and propranolol were restored to control values after a single injection of indomethacin (30mg/kg, i.p.). Membrane fractions, prepared from bronchial tissues and which sedimented between 280 g and 100,000 g, showed a high affinity for the radio ligand, 125I hydroxybenzylpindolol. 90% of the binding was displaced by 1-propranolol (EC50 value 10 minus to the 8th power M). d-propranolol was less effective in this regard (EC50 value 10 minus to the 6th power M). Phentolamine (up to 10 minus to the 3rd power M9 and phenoxybenzamine (up to 10 minus to the 5th power M) displaced less than 10% of the bound pindolol. In animals chronically treated with isoproterenol, the specific binding was reduced by 50%. The membrane fractions also showed adenylate cyclase activity 8pM cyclic AMP/minute/mg proteinin 2mM Mg 2 ions and 40pM cyclic AMP/minute/mg protein in 10mM Mg 2 ion. The stimulation by magnesium was reduced (50%) after chronic isoproterenol treatment. Prostaglandin production by airway smooth muscle is increased after ascorbic acid or isnproterenol treatments. Our data suggest a relationship between the loss of adrenergic binding sites and prostaglandin production.